Rufer N, Brümmendorf T H, Kolvraa S, Bischoff C, Christensen K, Wadsworth L, Schulzer M, Lansdorp P M
Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, British Columbia V5Z 1L3, Canada.
J Exp Med. 1999 Jul 19;190(2):157-67. doi: 10.1084/jem.190.2.157.
To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.
为了研究造血细胞中端粒长度随年龄的动态变化,我们分析了不同有核血细胞群体中端粒重复序列的平均长度。使用定量荧光原位杂交和流式细胞术对500多名年龄在0至90岁之间的个体进行了分析,其中包括36对同卵双胞胎和异卵双胞胎。粒细胞和初始T细胞的端粒长度随年龄呈现平行的双相下降,这很可能反映了这两种细胞类型的共同前体——造血干细胞中累积的细胞分裂。端粒丢失在第一年非常迅速,并以低30倍的速率持续了八十多年。记忆T细胞的端粒长度也随年龄最初迅速下降。然而,与初始T细胞不同的是,这种下降持续了数年,并且在老年个体中,淋巴细胞的端粒通常比粒细胞的端粒短。我们的研究结果表明,幼儿期干细胞更新急剧下降,并支持造血干细胞和T细胞中的细胞分裂导致端粒DNA丢失这一观点。